The purpose of the proposed research is two-fold: First, to study the cellular mechanisms of the biosynthesis of TRH, and secondly, to isolate and characterize several small polypeptides in the human placenta capable of stimulating the release of tropic hormones from the anterior pituitary. We propose to use a combination of analytical techniques such as mass spectrometry, amino acid analyzers and high pressure liquid chromatography to study the incorporation of radiolabelled precursors into TRH. It is hoped that this research will allow us to identify any possible prohormones and to determine the sequence of chemical events leading to the synthesis of TRH in the frog skin. Frog skin is an excellent model because of the large amounts of tru-TRH which it possesses, the ease of obtaining large amounts of tissue, and because of the skin's hardiness in an in vitro system. Our second aim concerns the further characterization of small placental polypeptides which are different from the classical hypothalamic releasing factors which we have recently discovered. It is our belief that further investigation of these molecules may help to uncover an as yet unsuspected means of communication between the placenta and the endocrine glands of either the fetus or the mother during pregnancy.